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Phase I Dose Escalation Study of Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy for Malignant Gliomas in Pediatric Patients


Phase 1
1 Year
18 Years
Not Enrolling
Both
Brain and Central Nervous System Tumors

Thank you

Trial Information

Phase I Dose Escalation Study of Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy for Malignant Gliomas in Pediatric Patients


OBJECTIVES:

Primary

- Determine the dose-limiting toxicity of adjuvant vaccination with autologous tumor
lysate-pulsed dendritic cells after surgical resection in pediatric patients with
malignant glioma.

- Determine the maximum tolerated dose of this vaccine in these patients.

Secondary

- Determine, preliminarily, the survival of patients treated with this vaccine.

- Determine, preliminarily, the time to tumor progression in patients treated with this
vaccine.

- Determine cellular immune response in patients treated with this vaccine.

- Determine age-dependent differences in response to this vaccine, in terms of
immunocompetence, in these patients.

OUTLINE: This is a dose-escalation study.

Patients undergo surgical resection to obtain tumor tissue for production of tumor lysate.
Patients then undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMC) for
generation of dendritic cells (DC). DC are pulsed with tumor lysate to produce an autologous
dendritic cell vaccine. Approximately 10-30 days after leukapheresis, patients receive
vaccination with autologous tumor lysate-pulsed dendritic cells intradermally on days 0, 14,
and 28 in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of vaccine until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed at 2 weeks and then every 2
months for 1 year.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study within 2-4.5
years.


Inclusion Criteria:



- Histologically confirmed* WHO grade III or IV malignant glioma of 1 of the following
subtypes:

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- Glioblastoma multiforme NOTE: *Must be confirmed after surgery

- Newly diagnosed OR recurrent disease

- Bidimensionally measurable disease by contrast-enhancing pre-operative MRI

- Surgically accessible tumor for which surgical resection is indicated at the time of
initial pre-operative evaluation

- Must have undergone standard surgery* AND either radiotherapy* or chemoradiotherapy*

- Objective evidence of disease by contrast-enhanced brain MRI after completion of
standard therapy NOTE: *Completed after study entry but before assignment to study
treatment cohorts

- Age 1 to 18

- Performance status Karnofsky 60-100%

- Hematopoietic

- Hemoglobin ≥ 10 g/dL

- Absolute granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hepatic

- SGPT and SGOT ≤ 2 times normal

- Alkaline phosphatase ≤ 2 times normal

- Bilirubin ≤ 1.5 mg/dL

- Hepatitis B and C negative

- Renal

- BUN ≤ 1.5 times normal OR

- Creatinine ≤ 1.5 times normal

- Immunologic

- HIV negative

- Syphilis negative

- At least 2 weeks since prior radiotherapy and recovered

- Negative pregnancy test

- Fertile patients must use effective contraception

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered

- No chemotherapy during and for 4 weeks* after the final dose of study vaccine

- No corticosteroids for at least 10 days before leukapheresis

- No concurrent corticosteroids

- More than 72 hours since prior systemic antibiotics

- No antihistamines for 5 days before and for 5 days after administration of study
vaccine

Exclusion Criteria:

- history of immunodeficiency or autoimmune disease that may be exacerbated by
immunotherapy, including any of the following:

- Rheumatoid arthritis

- Systemic lupus erythematosus

- Vasculitis

- Polymyositis

- Dermatomyositis

- Scleroderma

- Multiple sclerosis

- Juvenile-onset insulin-dependent diabetes

- active infection

- fever

- allergy to study reagents

- pregnant or nursing

- other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer, localized prostate cancer, or carcinoma in situ of the
cervix

- unstable or severe medical or psychiatric condition, as determined by the
investigator

- underlying condition that would preclude study participation

- concurrent radiotherapy

- prior organ allograft

- concurrent strong painkillers

- other concurrent immune-suppressing medications

- other concurrent investigational agents

- other adjuvant treatment for 4 weeks* after the final dose of study vaccine NOTE:
*Unless there is evidence of tumor progression necessitating additional
clinically-indicated treatment; patients requiring treatment due to tumor progression
are removed from the study

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity of adjuvant vaccination with autologous tumor lysate-pulsed dendritic cells after surgical resection in pediatric patients with malignant glioma.

Outcome Time Frame:

1 year

Safety Issue:

Yes

Principal Investigator

Joseph L. Lasky, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jonsson Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000420930

NCT ID:

NCT00107185

Start Date:

January 2005

Completion Date:

March 2010

Related Keywords:

  • Brain and Central Nervous System Tumors
  • childhood high-grade cerebral astrocytoma
  • recurrent childhood cerebral astrocytoma
  • childhood oligodendroglioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Glioma

Name

Location

Jonsson Comprehensive Cancer Center at UCLALos Angeles, California  90095-1781